Effects of enalapril maleate on blood pressure, renin-angiotensin-aldosterone system, and peripheral sympathetic activity in essential hypertension

Recent experimental studies showed that inhibition of angiotensin II synthesis may reduce sympathetic activity as evaluated by plasma catecholamine assay, sharing in the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors. Fifteen patients with essential hypertension were studied. Blood pressure and heart rate were evaluated both at rest and after stressor laboratory tests, before and four hours after administration of 20 mg of enalapril maleate and on the 14th and 120th days of continued administration. At the same time, blood samples were drawn for determinations of plasma renin activity, ACE, angiotensin II, plasma aldosterone concentration, and plasma norepinephrine levels. Enalapril in a dosage of 20 mg/day significantly and progressively lowered systolic and diastolic blood pressure at rest, with maximal decreases observed on the 120th day of the study period (P less than 0.001). Heart rate at rest and after exercise showed no significant differences throughout the study period. Good blood pressure control was observed during stressor laboratory tests. The greatest impact of blood pressure was observed on the 120th day during dynamic exercise (mean blood pressure from 139 +/- 3.9 to 111.5 +/- 6.3 mmHg; P less than 0.01) and on the 14th day during the cold pressure test (mean blood pressure from 133.3 +/- 3.9 to 111.2 +/- 4.7 mmHg; P less than 0.005). A marked and persistent ACE inhibition and a gradual and progressive decrease of angiotensin II (from 12.42 +/- 2.15 to 5.45 +/- 1.68 pg/ml; P less than 0.005) characterized the humoral activity of enalapril maleate. Moreover, a significant decrease of plasma norepinephrine levels was observed during the follow-up period with maximal reduction on the 120th day (from 311 +/- 34 to 197 +/- 33 pg/ml; P less than 0.01). It has been demonstrated that the pressor effect of angiotensin II was blunted during exercise. Our hemodynamic and humoral results appear to confirm the hypothesis that enalapril maleate may reduce blood pressure by direct inhibition of ACE and of kininase II as well as by a decreased sympathetic output, which may be secondary to angiotensin II inhibition. These results agree with the recent experimental demonstration of a reduced sympathetic nervous response to nerve stimulation during ACE inhibition.     

Antihypertensive therapy with Ca2+. Antagonist verapamil and/or ACE inhibitor enalapril in NIDDM patients.

OBJECTIVE: To assess the efficacy and tolerance of a diuretic-free antihypertensive therapy with a Ca2+ antagonist and an angiotensin-converting enzyme (ACE) inhibitor in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: After a 2-wk washout and a 4-wk placebo phase, 47 hypertensive patients with NIDDM randomly received verapamil or enalapril alone and, if blood pressure remained elevated, both agents combined over 30 wk. RESULTS: Verapamil or enalapril alone normalized blood pressure to less than 90 mmHg diastolic in 30 patients; verapamil decreased mean +/- SE blood pressure from 159/98 +/- 3/1 to 146/87 +/- 3/2 mmHg (n = 18, P less than 0.001) and enalapril from 166/99 +/- 5/2 to 146/86 +/- 3/1 mmHg (n = 12, P less than 0.001). In 17 patients who were still hypertensive after 10 wk of monotherapy, combination of both drugs decreased blood pressure from 170/104 +/- 4/2 to 152/90 +/- 4/2 mmHg (P less than 0.001). Fasting plasma glucose, glycosylated hemoglobin, serum fructosamine, total lipids, high-density and low-density lipoprotein cholesterol, apolipoproteins A-I and B, creatinine, and urinary albumin-creatinine ratio were not significantly modified. CONCLUSIONS: In hypertensive patients with NIDDM, a diuretic-free therapy based on the Ca2+ antagonist verapamil and/or the ACE inhibitor enalapril can effectively decrease blood pressure without adversely affecting carbohydrate and lipid metabolism.     

Effects of enalapril in insulin-dependent diabetic subjects with mild to moderate uncomplicated hypertension

The antihypertensive efficacy of enalapril and its effects on the metabolism and kidney function were investigated in 11 insulin-dependent diabetic subjects with uncomplicated mild to moderate hypertension. During a short-term single-blind controlled trial, one daily dose of 20 or 40 mg enalapril significantly reduced both systolic and diastolic blood pressure. In the supine position, mean systolic blood pressure declined from 169 +/- 6 to 142 +/- 6 mmHg (P less than .01) and mean diastolic blood pressure from 101 +/- 1.5 to 85 +/- 2 mmHg (P less than .001). No changes in heart rate or postural hypotension were observed. During 1 yr of treatment, the antihypertensive efficacy of enalapril did not decline, and no clinical side effects were observed. Inhibition by enalapril of angiotensin-converting enzyme did not modify daily insulin requirements, glycemic control, uricemia, or lipid metabolism; kalemia and the markers of diabetic nephropathy were not significantly altered. These results suggest that enalapril once daily should be used as the first step in the treatment of diabetic patients with mild to moderate hypertension.     

Importance of Heart Rate Modulation on the Cardiac Hemodynamics During Postexercise Recovery

The influence of heart rate changes on the recovery of cardiac hemodynamics and lactate clearance after exercise was studied in nine patients with complete atrioventricular (AV) block treated with programmable pacemakers. A preliminary treadmill exercise test in which the pacing rate was externally increased stepwise from 70 to 130 bpm was performed to determine the maximum exercise duration. Two exercise tests involving an equal amount of exercise load were performed, the pacing rate was either programmed to the basic rate (abrupt decay) or gradually (modulated decay) immediately after exercise termination. Compared with abrupt decay, modulated decay resulted in a higher mean arterial pressure (100 +/- 4 mmHg vs 91 +/- 5 mmHg, P less than 0.05) and diastolic pressure (76 +/- 4 mmHg vs 59 +/- 4 mmHg, P less than 0.001) immediately on exercise termination. Immediately after exercise and during modulated decay, cardiac output (represented by Doppler derived minute distance) declined gradually and was determined mainly by a higher pacing rate without significant changes in stroke volume. On the other hand, minute distance fell abruptly during abrupt decay (996 +/- 107 m at peak exercise and 561 +/- 88 m immediately after a rate change at exercise termination, P less than 0.01) with a corresponding abrupt increase in systemic vascular resistance. This was later compensated by a gradual increase in stroke volume during the recovery period. The cumulative cardiac output between the two rate changes equalized at the 4th minute of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ketanserin in mild to moderate hypertension in the elderly: a double-blind study versus methyldopa

In a double-blind study of 30 elderly patients with mild to moderate essential hypertension, the antihypertensive effects of ketanserin and methyldopa were compared. The patients were randomly assigned to receive 20 mg of ketanserin or 250 mg of methyldopa twice daily for two weeks; the dose was then doubled for the rest of the three-month period. Two of the ketanserin group dropped out of treatment, one because of psychic depression, the other because of epigastric pain. After three months of therapy with ketanserin, systolic blood pressure decreased in a dose-dependent manner from 190 +/- 20 to 175 +/- 20 mmHg (P less than 0.05) and diastolic blood pressure from 106 +/- 8 to 91 +/- 9 mmHg (P less than 0.001). Blood pressure was reduced to 160/90 mmHg or less in eight of the 13 ketanserin patients and in five of the 15 methyldopa patients. In both groups heart rate and body weight remained constant. No orthostatic hypotension or hypertensive rebound after ketanserin withdrawal was recorded. It is concluded that 40 mg of ketanserin twice daily can control hypertension in the elderly.     

Effect of isometric exercise and autonomic blockade on the haemodynamics: a noninvasive study in healthy volunteers

Sixteen healthy young volunteers were studied with echocardiography and systolic time intervals at rest and after three minutes' isometric exercise before and during autonomic blockade with atropine and propranolol. Isometric exercise increased cardiac output by raising the heart rate from 64 +/- 3 to 72 +/- 4 bpm (SEM) (p less than 0.01). Mean blood pressure increased from 86 +/- 2 to 104 +/- 3 mmHg (p less than 0.001) without any changes in the calculated total peripheral vascular resistance. Afterload (left ventricular systolic wall stress) rose but preload (left ventricular end-diastolic diameter, LVEDD) did not change. There was no variation in fractional shortening, maximal velocity of circumfertial fibre shortening (VCFmax) or pre-ejection period (PEP) despite increased afterload. This indicates stimulated intropy during isometric exercise. Autonomic blockade enhanced cardiac output by increasing heart rate from 64 +/- 3 to 97 +/- 2 bpm (p less than 0.001). Mean blood pressure rose from 86 +/- 2 to 93 +/- 2 mmHg (p less than 0.01) while vascular resistance fell. Afterload did not change but LVEDD shortened form 45.5 +/- 0.9 to 43.5 +/- 0.9 mm (p less than 0.001). Preload-independent VCFmax did not increase despite raised heart rate. PEP rose from 99 +/- 4 to 107 +/- 3 ms (p less than 0.01) and fractional shortening fell from 29 +/- 1 to 25 +/- 1% (p less than 0.001); these changes were greater than expected from the reduced preload. Consequently autonomic blockade seems to impair myocardial contractility despite vagal dominance at rest. Heart rate and cardiac output were not influenced by isometric exercise during autonomic blockade.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise blood pressure and baroreflex function in borderline hypertensive and normotensive young men

1. Resting carotid baroreflex sensitivity and blood pressure responses to standardized conditions of rest and exercise were measured in 17 borderline hypertensive males and 12 normotensive males. 2. The borderline hypertensive group had significantly higher systolic and diastolic blood pressures during orthostatic rest and isometric handgrip exercise and higher systolic blood pressure during supine rest and submaximum and maximum treadmill exercise. 3. The borderline hypertensive group had an attenuation of baroreflex sensitivity compared with the normotensive group. Resting baroreflex sensitivity was significantly correlated with absolute systolic blood pressure during supine rest, orthostatic rest, isometric handgrip exercise and submaximum treadmill exercise. 4. The results indicate that blood pressure is regulated at a significantly higher level during rest and exercise in borderline hypertension and is associated with reduced baroreflex sensitivity measured at supine rest.     

Haemodynamic and hormonal responses to exercise: Studies in patients with diabetes mellitus and adrenomedullary deficiency

The haemodynamic and hormonal responses of patients with autonomic neuropathy and others with adrenomedullary deficiency were compared with mild hypertensives (range of blood pressure 90-100 mmHg diastolic and 140-160 mmHg systolic) and uncomplicated diabetics during standard exercise and postural manoeuvres using continuous arterial blood pressure monitoring. There was no difference in these parameters between the groups when at rest or on standing. During exercise there was no significant difference in blood pressure and heart rate between the groups and all showed significant increases in plasma noradrenaline (mean rise for all groups 2730-22 105 pm 1(-1), P less than 0.03) and (in all but the adrenalectomized subjects) adrenaline (mean rise for remaining three groups 946-3384 pm 1(-1), P less than 0.03; adrenalectomized group showed no rise). The group with autonomic neuropathy showed a significant rise in plasma cortisol from basal 450 +/- 40 to 845 +/- 72 nm 1(-1), P less than 0.005 after exercise, but the other groups showed no significant change. The maximum level attained for plasma cortisol in the adrenalectomized subjects after exercise was significantly less (260 +/- 41 nm 1(-1) than in the diabetic groups (696 +/- 68 nm 1(-1) (non-neuropaths), 845 +/- 72 nm 1(-1) (neuropaths), P less than 0.01). We have demonstrated normal blood pressure and pulse responses to posture and sustained exercise in diabetics with autonomic neutropathy. The findings of similarly normal responses in patients with adrenomedullary deficiency suggest that circulating adrenaline is not obligatory to a normal haemodynamic response to exercise.     

Rectal administration of nifedipine: haemodynamic effects and pharmacokinetics in hypertensives

The haemodynamic effects and pharmacokinetics of nifedipine suppositories, used mainly for hypertensive emergencies, were studied in 10 severely hypertensive patients. Following rectal administration, significant hypotensive effects occurred after 0.5 h and lasted until 7 h after administration. The mean (+/- SE) maximum decreases in systolic and diastolic blood pressures 1.5 h after administration were: systolic, 61.8 +/- 7.9 mmHg (P less than 0.001); and diastolic, 30.8 +/- 4.0 mmHg (P less than 0.001). No serious side-effects were reported and heart rate did not change significantly. Mean nifedipine concentration in the blood peaked at 52.4 ng/ml, 1 h after administration and, after 7 h, was still 14.3 ng/ml which is higher than the minimum plasma concentration required for hypotensive effects to occur. There was a close correlation between nifedipine concentration in the blood and hypotensive effects. These results indicate that rectal administration of nifedipine should be regarded as a useful alternative treatment in hypertensive emergencies.     

Changes in blood pressure during the normal menstrual cycle.

1. Changes in blood pressure during the normal menstrual cycle are not well documented, and previous studies have given conflicting results. 2. Thirty normotensive women and ten mildly hypertensive women measured their blood pressure at home each morning for 6 weeks, under standardized conditions, using a UA-751 semi-automatic sphygmomanometer. All had normal menstrual cycles and subjects entered the study at different phases of the cycle. 3. Blood pressure was higher at the onset of menstruation than at most other phases of the cycle (systolic blood pressure, P less than 0.05; diastolic blood pressure, P less than 0.001). Adjusted diastolic blood pressure was higher in the follicular than in the luteal phase (mean difference 1.23 mmHg, P less than 0.001). Similarly, blood pressure was lower during days 17-26 than during the remainder of the cycle (adjusted mean difference in systolic blood pressure -0.65 mmHg, P = 0.07; adjusted mean difference in diastolic blood pressure -1.19 mmHg, P less than 0.001). 4. Similar patterns were seen in normotensive and hypertensive subjects, and changes in plasma 17 beta-oestradiol and progesterone concentrations were also similar in the two groups.     

Decreased exercise heart rate and blood pressure response in diabetic subjects with cardiac autonomic neuropathy

Abnormal hemodynamic responses to exercise have been observed in diabetic subjects, but the pathogenesis and significance remain uncertain. We used maximal treadmill exercise to study 32 subjects with long-term insulin-dependent diabetes without clinical evidence of cardiac disease. Two of the 32 had occult ischemic heart disease revealed by stress electrocardiography and myocardial-perfusion scintigraphy and were excluded from subsequent analysis. In the remaining 30 subjects, we compared the responses to exercise of the 17 subjects with cardiac autonomic neuropathy diagnosed by noninvasive maneuvers (group 1) with the 13 without (group 2). At rest, the pressure-rate product (PRP) was higher in group 1 (114.0 +/- 5.7 vs. 95.9 +/- 5.3, P less than .05). With maximal exercise the increase in heart rate (44.6 +/- 4.8 vs. 79.0 +/- 5.4 beats/min, P less than .001), systolic blood pressure (36.8 +/- 5.9 vs. 55.0 +/- 5.8 mmHg, P = .02), and the PRP (102.0 +/- 7.3 vs. 182.0 +/- 8.2, P less than .001) were all lower in group 1 than in group 2, despite similar total treadmill times (631 +/- 47 vs. 587 +/- 40 s, P greater than .1). At each stage of exercise, the increase in heart rate and systolic blood pressure was lower in group 1 patients. The severity of cardiac autonomic neuropathy correlated inversely with the maximal increase in heart rate (r = -.68, P less than .001) and the PRP (r = -.58, P less than .005). Age, duration of diabetes, and the presence and severity of microvascular disease did not correlate with any of the hemodynamic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of nipradilol, a new beta-blocking agent with vasodilating properties, on exercise tolerance in patients with stable effort angina: a double-blind study

The effects of nipradilol, a new beta-blocking agent with vasodilating properties, on exercise tolerance were examined in eight patients with stable effort angina. Symptom-limited treadmill tests were performed two hours after administration of oral nipradilol (9 mg) or placebo in a double-blind manner. Exercise time to the onset of angina was significantly longer after nipradilol than after placebo (6.8 +/- 2.5 min versus 5.0 +/- 1.2 min, P less than 0.05). Exercise duration after nipradilol was not statistically different from that after 0.3 mg of sublingual nitroglycerin (7.2 +/- 1.9 min). Nipradilol significantly decreased heart rate both at rest and during exercise (P less than 0.01). Systolic blood pressure at rest did not change after nipradilol. However, an increase in systolic blood pressure during exercise was inhibited by nipradilol. The pressure rate product was significantly lower after nipradilol than after placebo. It is concluded that nipradilol improves exercise tolerance in patients with stable effort angina by decreasing the myocardial oxygen consumption during exercise.     

Effects of chronic cetamolol therapy on resting, ambulatory, and exercise blood pressure and heart rate

We studied blood pressure (BP) and heart rate (HR) responses in 12 patients with hypertension who were receiving cetamolol, a cardioselective beta-blocker with intrinsic sympathomimetic activity. The BP and HR parameters were evaluated at rest (casual, office readings), with ambulatory BP monitoring, and after treadmill exercise testing. At a mean (+/- SD) dose of 46 +/- 21 mg/day, casual supine BP decreased by 10/12 mm Hg (P less than 0.05 for systolic; P less than 0.01 for diastolic) compared with placebo, while HR decreased 4 bpm. Cetamolol resulted in a significant reduction in the mean 24-hour systolic BP. The most striking reduction occurred in the BP at work (23 mm Hg), with almost no decrease in the BP during sleep. Ambulatory HR reductions occurred while the subjects were at work (9 bpm; P less than 0.05) but not while at home (awake) or during sleep. The mean duration of exercise was the same during cetamolol and placebo phases, but both HR and BP fell significantly at peak performance after cetamolol. These data suggest that cetamolol reduces BP without lowering HR at rest. During periods of increased adrenergic activity such as work and dynamic exercise, both HR and BP are reduced.     

Haemodynamic responses to static and dynamic handgrip before and after autonomic blockade

1. Six healthy men performed static and dynamic handgrip to local muscular fatigue in approximately 6 min under control conditions, i.e. without drugs and after combined parasympathetic and beta-adrenergic blockade with atropine and metoprolol. 2. From rest to exercise at fatigue, systolic, diastolic and mean arterial pressures increased by 32 +/- 4 and 39 +/- 3 mmHg, 24 +/- 3 and 26 +/- 4 mmHg, and 26 +/- 3 and 30 +/- 3 mmHg respectively for static and dynamic handgrip. There were no significant differences between the pressor responses for the two modes of contraction. Cardiac output increased significantly only during dynamic exercise. Total peripheral resistance increased by 2.3 +/- 1.0 units for static handgrip (P less than 0.05) and by 0.7 +/- 0.8 unit (P greater than 0.05) for dynamic handgrip. Autonomic blockade abolished the heart rate response to both static and dynamic handgrip. For both modes of contraction the systolic arterial pressure responses were 9-12 mmHg lower (P less than 0.05) after autonomic blockade, but the diastolic and mean pressure responses were not significantly affected. A significant increase in cardiac output persisted during dynamic exercise. The increase in peripheral resistance during static exercise tended to be greater after blockade. Plasma noradrenaline and adrenaline levels showed only minor elevations in response to static and dynamic handgrip and were not changed by autonomic blockade. 3. These data indicate that when performed to a common end-point with identical small muscle groups static and dynamic exercise produce an equally large pressor response, which is only slightly attenuated by autonomic blockade.     

Hypertensive stress increases dispersion of repolarization

Several electrocardiographic indices for repolarization heterogeneity have been proposed previously. The behavior of these indices under two different stressors at the same heart rate (i.e., normotensive gravitational stress, and hypertensive isometric stress) was studied. ECG and blood pressure were recorded in 56 healthy men during rest (sitting with horizontal legs), hypertensive stress (performing handgrip), and normotensive stress (sitting with lowered legs). During both stressors, heart rates differed <10% in 41 subjects, who constituted the final study group. Heart rate increased from 63 +/- 9 beats/min at rest to 71 +/- 11 beats/min during normotensive, and to 71 +/- 10 beats/min during hypertensive stress (P < 0.001). Systolic blood pressure was 122 +/- 15 mmHg at rest and 121 +/- 15 mmHg during normotensive stress, and increased to 151 +/- 17 mmHg during hypertensive stress (P < 0.001). The QT interval was larger during hypertensive (405 +/- 27) than during normotensive stress (389 +/- 26, P < 0.001). QT dispersion did not differ significantly between the two stressors. The mean interval between the apex and the end of the T wave (Tapex-Tend) of the mid-precordial leads was larger during hypertensive (121 +/- 17 ms) than during normotensive stress (116 +/- 15 ms, P < 0.001). The singular value decomposition T wave index was larger during hypertensive (0.144 +/- 0.071) than during normotensive stress (0.089 +/- 0.053, P < 0.001). Most indices of repolarization heterogeneity were larger during hypertensive stress than during normotensive stress. Hypertensive stressors are associated with arrhythmogeneity in vulnerable hearts. This may in part be explained by the induction of repolarization heterogeneity by hypertensive stress.     

Beat-to-beat heart rate adaptation in pediatric and late adolescent patients with closed loop rate-responsive pacemakers

The aim of this study was to evaluate the efficacy of physiological rate-responsive pacemakers (Closed Loop Stimulation--CLS) to pace pediatric and late adolescent patients undergoing rest, mental, standing, and exercise testing. Dual-chamber pacemaker is increasingly indicated for young patients. A new physiological pacing mode based on the indirect measure of ventricular contractility (CLS), has shown interesting results in adults, while no data on pediatric patients are available. RR intervals and beat-to-beat systolic and diastolic pressures were monitored in 12 pediatric patients (6 males, mean age 17 years [12-22 years]) who had a transvenous implant of Inos2+-CLS dual-chamber pacemaker (Biotronik GmbH, Berlin, Germany) and endocardial leads. All the patients showed correct electrical parameters at the implant and during the follow-ups. Paced RR intervals decreased significantly (F = 7.28, P = 0.01) from 0.85 +/- 0.08 seconds (rest) to 0.73 +/- 0.10 seconds (mental) and to 0.75 +/- 0.010 seconds (standing); systolic/diastolic pressure was significantly higher (F = 12.2, P = 0.002/F = 13.6, P = 0.001) in mental (134.4 +/- 19.9/74.4 +/- 8.1 mmHg) with respect to rest (115.1 +/- 18.3/61.0 +/- 6.1 mmHg), and standing (118.7 +/- 23.9/67.3 +/- 0.1 mmHg). During exercise the paced RR interval showed significant decrease of about 35% from baseline to maximum load (F = 24.90, P = 0.001) and systolic pressure increased significantly (F = 4.91, P = 0.019) by about 34% from baseline to maximum load. The comparison between paced and spontaneous rates showed very similar values and trend. In addition, CLS mode does not seem to overrun the spontaneous heart activity, when present. This is a study to evaluate CLS pacing in pediatric and late adolescent patients. The study shows that CLS pacing responds to both physical and non-physical stressors, providing physiological pacing rates, as previously observed in adults.     

Comparative efficacy of perindopril and enalapril once daily using 24-hour ambulatory blood pressure monitoring

ACE inhibitors are important therapeutic agents in controlling hypertension, correcting some of its pathophysiological derangement and improving its prognosis. While there are many such agents, there may be some important differences between them. This placebo run-in, double blind, crossover study, using 24-hour ambulatory blood pressure monitoring, compares the efficacy of perindopril 4-8 mg and enalapril 10-20 mg as once daily antihypertensive agents on 32 patients. For diastolic blood pressure (DBP), perindopril had a placebo-corrected peak (P) reduction of blood pressure (BP) of -6.4 +/- 1.3 mmHg vs its placebo-corrected trough (T) of -5.2 +/- 1.7 mmHg. Enalapril had a reduction in DBP of -8.5 +/- 1.3 mmHg (P) and -5.7 +/- 1.7 mmHg (T). For systolic blood pressure (SBP), perindopril had a reduction of -7.5 +/- 1.6 mmHg (P) vs -7.3 +/- 2.2 mmHg (T) compared to enalapril with -10.8 +/- 1.6 mmHg (P) vs -8.3 +/- 2.3 mmHg (T). Placebo-corrected trough-to-peak ratio (SBP/DBP) for perindopril was 0.97/0.81 vs 0.77/0.67 for enalapril. There was no difference noted in 24-hour mean BP, area under the curve or post-dose casual BP measurements. Both perindopril and enalapril were well tolerated and the two treatment groups had similar safety profiles. Perindopril thus had a predictable and sustained blood pressure effect giving a 24-hour cover for the patient without excessive peak effect or poor trough effect.     

Exercise-induced hypertension in normotensive patients with NIDDM

The aim of this study was to determine whether blood pressure during mild to moderate exercise is abnormal in patients with non-insulin-dependent diabetes mellitus (NIDDM). The study group consisted of 11 patients with NIDDM and 11 nondiabetic subjects of comparable age and body mass index. All subjects were sedentary and basally normotensive. Bicycle ergometry was used to assess the effect of exercise on blood pressure at a steady state of 70-75 W, with a target duration of 20 min. Blood pressure was measured basally and every 5 min. Greater exercise-induced systolic blood pressure (mean max 208.0 +/- 6.0 vs. 177.0 +/- 3.0 mmHg) occurred in the NIDDM group (P less than 0.001). Neither pulse rate nor diastolic blood pressure differed between the groups before or during exercise. Return to basal pulse and blood pressure was similar. Mild to moderate exercise induces greater systolic blood pressure in sedentary patients with NIDDM. Because exercise is recommended as one therapeutic modality, intraexercise blood pressure should be considered in assessing the safety of this form of treatment.     

Reflex increase in blood pressure during the intracoronary administration of adenosine in man.

Infusion of adenosine (0.022-2.2 mg/min) into the left anterior descending (LAD) coronary artery of 26 patients produced a dose-dependent increase in blood pressure without a change in heart rate. At adenosine 2.2 mg/min, systolic pressure rose by 21.0 +/- 2.2 mmHg from 134 +/- 4.3 mmHg (P less than 0.001) and diastolic pressure increased by 10.4 +/- 1.1 mmHg from 76 +/- 1.9 mmHg (P less than 0.001). The rise in arterial pressure was associated with a 22 +/- 3.4% increase in systemic vascular resistance (P less than 0.01) and no change in cardiac output (-2.8 +/- 4.3%, P = NS). Plasma norepinephrine levels rose by 40 +/- 14% from 105 +/- 9 pg/ml (P less than 0.05) and epinephrine levels by 119 +/- 31% from 37 +/- 9 pg/ml (P less than 0.01). Right atrial infusion of adenosine produced insignificant hemodynamic effects, suggesting that systemic spillover of adenosine was not responsible for the observed effects. In 20 cardiac transplant patients with denervated hearts, LAD infusion of adenosine (2.2 mg/min) produced no change in systolic pressure (-0.1 +/- 1.6 mmHg from 139 +/- 3.4 mmHg, P = NS) and a decrement in diastolic pressure (-4.7 +/- 1.2 mmHg from 98 +/- 2.5 mmHg, P less than 0.01). Thus, infusion of adenosine into the LAD coronary artery causes a reflex increase in arterial pressure due to a rise in systemic vascular resistance, probably as a result of increased sympathetic discharge. This reflex pathway may be of importance in disease states such as myocardial ischemia, in which myocardial adenosine levels are elevated.     

Muscle afferent and central command contributions to the cardiovascular response to isometric exercise of postural muscle in patients with mild chronic heart failure

The roles of muscle afferent activity and central drive in controlling the compromised cardiovascular system of patients with mild chronic heart failure (CHF) during isometric exercise were examined. Blood pressure and heart rate responses were recorded in eight stable CHF patients (ejection fraction 20-40%; age 62+/-11 years) and in nine healthy age-matched controls during voluntary and electrically evoked isometric plantar flexion and subsequent post-exercise circulatory occlusion (PECO). During voluntary contraction, control subjects had a greater mean increase in systolic blood pressure than patients (42.4+/-19.2 and 23.0+/-10.9 mmHg respectively; P<0.01), but this was not the case during PECO. During electrically evoked contraction, but not during PECO, the CHF group had smaller (P<0.05) mean increases in both systolic and diastolic blood pressure than controls (13.0+/-5.3 compared with 25.4+/-14.0 mmHg and 7.6+/-3.0 compared with 12.9+/-7.2 mmHg respectively). Intra-group comparison between responses to voluntary and electrically evoked contractions revealed greater (P<0.05) mean increases in systolic and diastolic blood pressure during the voluntary contraction in both the patients and the control subjects. These data suggest that muscle afferent drive to the pressor response from the triceps surae is low in this age group, both in control subjects and in CHF patients. Additionally, the patients may have a relatively desensitized muscle mechanoreceptor reflex.